# Kinases as Therapeutic Targets for Endometriosis

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2022 · $687,714

## Abstract

ABSTRACT
The human genome encodes 538 protein kinases, most of which are functionally important and are involved in
the pathogenesis of many diseases. This new R01 is a discovery-based grant focused on the molecular
validation of novel kinases that are upregulated in endometriosis. To address new therapeutic options for
endometriosis, we will validate a subset of endometriosis-implicated kinases using siRNA knockdown
strategies and available small molecule inhibitors and subsequently use DNA-Encoded Chemistry Technology
(DEC-Tec) to identify novel therapeutic molecules for further chemical validation in vitro and in vivo. We
identified dozens of kinases that are statistically upregulated in the lesions of patients with ovarian
endometriosis, peritoneal endometriosis, and/or deep infiltrating endometriosis compared to control and patient
endometrium. The hypothesis for this R01 is that inhibition of one or more of these novel kinase targets will be
effective in the treatment of endometriosis. In this proposal, we outline a comprehensive approach to
functionally characterize and target kinases in primary endometriotic stromal cells and organoid cultures
derived from women. In parallel, we will utilize state-of-the-art DEC-Tec selection methods available in the
Center for Drug Discovery (CDD) at Baylor College of Medicine (BCM) to identify novel kinase inhibitors that
will then be re-synthesized without the DNA barcode and chemically optimized by our team. We currently have
a screening collection of over 6 billion DNA-encoded molecules. The overarching objective is to identify potent
and selective kinase inhibitors that can provide a foundation for new medicines to address the unmet clinical
needs of endometriosis patients. The Specific Aims are: 1) Perform target validation of overexpressed kinases;
2) Use DEC-Tec to identify novel small-molecule inhibitors of validated kinases and optimize the selectivity,
activity, and stability of high affinity kinase binders; and 3) Evaluate optimized high affinity kinase inhibitors in
vitro and in vivo. Identifying new efficacious therapies for endometriosis requires a multifaceted approach that
necessitates increased efforts to identify and screen novel targets for drug discovery. Our approach, which
combines gene expression datasets for target identification with a novel DEC-Tec drug discovery platform, will
rapidly advance key kinase targets through a well-established drug discovery pipeline. Our multidisciplinary
team is seeking to discover new chemical entities that address the non-hormonal axes of endometriosis as
stand-alone therapy or as sequential therapy during hiatus from endocrine-suppressing agents. Our DEC-Tec
platform will help us to find the first specific inhibitors of unexplored kinases (a major druggable class of
proteins) that are elevated in endometriosis to dissect these key physiological pathways and pathological
mechanisms underlying endometriosis and provide new disease-specific treatm...

## Key facts

- **NIH application ID:** 10532966
- **Project number:** 1R01HD110038-01
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** MARTIN M. MATZUK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $687,714
- **Award type:** 1
- **Project period:** 2022-08-01 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10532966

## Citation

> US National Institutes of Health, RePORTER application 10532966, Kinases as Therapeutic Targets for Endometriosis (1R01HD110038-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10532966. Licensed CC0.

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